rTMS in Wilson Disease Dysarthria

NCT ID: NCT04910581

Last Updated: 2024-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-23

Study Completion Date

2024-01-12

Brief Summary

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Wilson disease is a hereditary hepatic and neurological disease associated with copper accumulation. Neurological symptoms are of extra-pyramidal, cerebellar and dystonic origin. Dysarthria is one of the debilitating symptoms of Wilson disease poorly responsive to pharmacological treatment. The most common form is a dystonic hyperkinetic Dysarthria.

Pathophysiology of dystonia is still not elucidated. Motor cortex hyperexcitability has been demonstrated in various forms of dystonia. Furthermore, rTMS inhibitory applied over motor cortex has been shown to transitory reduce dystonic symptoms in various forms of dystonia.

In the present study, we investigate the effect of a single 1Hz 20-minutes inhibitory rTMS session applied over the motor laryngeal cortex on dyasarthria is the main kinetic dysarthria has been shown to be associated with inhibition of laryngeal motor cortex in Parkinson disease.

Detailed Description

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A consecutive series of Wilson disease patients with dystonic hyperkinetic dysarthria will be prospectively recruited.

Patients will receive 3 days apart to two rTMS sessions.

rTMS procedures will be performed with a figure of eight coiled. A single 20-minutes 1 Hz biphasic stimulation (1200 pulses) session will be applied over the laryngeal motor cortex. A brain imaging positioning device will be used during all the procedure A second stimulation session will be performed 3 days apart.

Patients will be centrally randomized to receive first either the active stimulation (80% of the resting motor threshold) or the sham stimulation (using a visually identical coil to reproduce the click sound and the scalp sensation of the active coil).

A TMS evaluation of cortical silent period over the left motor cortex will be performed before the first rTMS session.

Before and immediately after each stimulation (active or sham) patient will received an clinical evaluation including Clinical Assessment Battery for Dysarthria intelligibility score, "A" phonation time, diadococinesia , bucco-linguo-facial motricity score and UWDRS.

A standard 20-minutes EEG will be performed before the first rTMS session and immediately after the second rTMS session.

Conditions

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Wilson Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

After randomization, patients are to receive blindly the first rTMS session according to the arm (placebo or active). A second stimulation session is to be performed 3 days apart to apply the reverse arm.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Patients are centrally randomized to receive first either the active stimulation (80% of the resting motor threshold) or the sham stimulation (using a visually identical coil to reproduce the click sound and the scalp sensation of the active coil). The operator is unblided. The evaluator is blinded.

Study Groups

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Experimental stimulation

Patients receive an inhibitor treatment of rTMS using activ coil (MCF B65 coil) for 30 minutes at 1Hz at 80% of the resting motor threshold (MagPro stimulator; MagVenture A / S, Farum, Denmark) onto the left laryngeal cortex located thanks to a neuronavigation device (Syneika one \[SYN1\], Syneika, Cesson-Sévigné, France).

Group Type ACTIVE_COMPARATOR

rTMS

Intervention Type PROCEDURE

Single 30-minutes session of 1Hz rTMS applied over the left laryngeal motor cortex

Sham stimulation

Patients receive a treatment of rTMS using placebo coil (MCF P B65 coil) for 30 minutes at 1Hz (MagPro stimulator; MagVenture A / S, Farum, Denmark) onto the left laryngeal cortex located thanks to a neuronavigation device (Syneika one \[SYN1\], Syneika, Cesson-Sévigné, France).

Group Type PLACEBO_COMPARATOR

Sham stimulation

Intervention Type PROCEDURE

Single 30-minutes session of sham stimulation applied over the left laryngeal motor cortex

Interventions

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rTMS

Single 30-minutes session of 1Hz rTMS applied over the left laryngeal motor cortex

Intervention Type PROCEDURE

Sham stimulation

Single 30-minutes session of sham stimulation applied over the left laryngeal motor cortex

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Conseting adult patients with social insurance
* Wilson disease with dystonic hyperkinetic dysarthria
* Stable pharmacological therapy n the last 6 monts
* Brain MRI in the previous 6 months, without additional brain lesion
* Patients that did not receive botulinium toxin in the previous 4 months

Exclusion Criteria

* Incapacitated adult
* Previous mdedical history of epilepsia
* Pregnancy or breastfeeding
* Brain lesion outside basal ganglia on brain MRI
* Patient consider by the investigator not able to sustain an 30 minutes rTMS session without moving
* Vocal chord lesion
* Previous history of laryngeal surgery
* rTMS contra indication
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Service de Physiologie Clinique-Explorations Fonctionnelles, AP-HP, Hôpital Lariboisière

Paris, , France

Site Status

Service de Neurologie, Hopital Fondation Adolphe de Rothschild

Paris, , France

Site Status

Countries

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France

Other Identifiers

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D20180404

Identifier Type: -

Identifier Source: org_study_id

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